Field of the Disclosure
The disclosure generally relates to the formation of metal nanoparticles (e.g., gold nanoparticles) using a carbohydrate capping agent (e.g., dextrin). The metal nanoparticles can be in the form of a metal nanoparticle core stabilized by the carbohydrate capping agent. Alternatively, the metal nanoparticles can be in the form of a nanoparticle core having a metal coating in a core-shell configuration, where the metal shell is stabilized by the carbohydrate capping agent. The metal nanoparticles are formed by reduction of a metal precursor at a neutral or alkaline pH in the presence of the carbohydrate capping agent, and optionally a nanoparticle core material. The carbohydrate capping agent provides a stabilized aqueous suspension of the metal nanoparticles. The metal nanoparticles can be used for detection of an analyte by functionalization of the nanoparticles with a binding pair member specific to the target analyte of interest.
Brief Description of Related Technology
Gold nanoparticles (AuNPs) have attracted considerable interest in recent years due to their wide range of application, for example in sensing methods as tracers and transducers. The spectral, electrical and chemical properties make AuNPs suited for sensing, molecular labeling, and bio-engineering (Li et al. 2002; Rechberger et al. 2003). Sensing technologies utilizing AuNPs include oxidation-reduction potentiometry, conductors in electrical circuits, and spectral reporters (2-100 nm) in solution (Dudak 2009; Pal et al. 2007; Xiliang et al. 2006). The sensing methodologies using AuNPs rely on attached surface biomolecules as recognition materials. The ligands (DNA, proteins, polymer, peptides, and antibodies) act as capping agents to stabilize the AuNP in aqueous solution and provide surface functionality, biological capture and chemical reactivities (Chah et al. 2005; Goluch et al. 2006; Hill and Mirkin 2006; Slocik et al. 2005; Zhou et al. 2009).
The most common AuNP synthesis techniques utilize citrate under acidic reaction conditions. Common methodologies for AuNP synthesis are: 1) non-polar synthesis using the Brust method (Brust et al. 1994), 2) aqueous generation with the Turkevich method (Turkevich et al. 1951), and 3) biological synthesis using microbial agents (Ahmad et al. 2003; Bharde et al. 2007; Das et al. 2009). Aqueous generation has been under study due to the “greener” nature of water-based reactions in comparison to non-polar solvents. The basic chemistry of formation for citrate reduction techniques is to reduce the Au3+ ion to Au0 and stabilize the surface of the colloidal gold with a capping molecule that is soluble in the synthesis media (Daniel and Astruc 2004). Traditional aqueous synthesis involves low pH and/or high temperatures; which limit the number of biological capping agents, requiring a ligand exchange step after synthesis for sensing applications.
Neutral to alkaline synthesis methods have been explored using microbial synthesis (Bharde et al. 2007; Das et al. 2009), sodium hydroxide reduction (Zhou et al. 2009) and sodium borohydride reactions (Brust et al. 1994). The appeal of microbial synthesis is that biological ligands (proteins, carbohydrates, glyco-lipids) are present during generation in an aqueous medium and could be used as the capping agent but have not shown the same control, stability and consistency of generation as current techniques for AuNP production (Torres-Chavolla 2010). Several biological agents have been explored for the reduction and capping of [AuCl4]− to produce gold colloids, including cysteine (Ma and Han 2008), tryptophan (Selvakannan et al. 2004), and ascorbic acid (Andreescu et al. 2006). The standard Burst technique of sodium borohydride formation requires a non-polar generation and a phase exchange for water soluble functionalization. Recent studies have explored the use of polymers for capping agents with sodium hydroxide as the reduction agent; but have not explored biomolecule attachments (Zhou et al. 2009). The reaction pH in most of these methods is within the acidic range and the resulting AuNP size is between 30-80 nm. Limited exploration of citrate has been conducted in alkaline conditions but reported as extremely slow and still requires post production ligand exchange (Ji et al. 2007).
Glyconanoparticles (carbohydrate functionalized nanoparticles) have recently been explored for carbohydrate-carbohydrate and carbohydrate-protein interaction studies, and for applications in biomedicine, including bio-labeling and biosensors (Aslan et al. 2005; de la Fuente and Penades 2006). Gold glyconanoparticles (AuGlycoNP) can be synthesized using a modification of the Brust methodology using one of several mono and disaccharides (e.g. lactose, maltose, and glucose) (de la Fuente and Penades 2006) for post production attachment with a ligand exchange technique. Recent work has successfully used cyclodextrin, dextrin, and glucose as aqueous capping agents after organic media production (Huang et al. 2004; Porta and Rossi 2003).